Key points from the evidence

The content of this evidence summary was up-to-date in January 2015. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Fostair NEXThaler is an inhaled corticosteroid (ICS)/ long‑acting beta‑2 agonist (LABA) combination dry powder inhaler containing extrafine beclometasone/formoterol. Evidence from an 8‑week randomised controlled trial suggests that in adults with stable asthma it is non‑inferior to the pressurised metered dose inhaler (Fostair), and superior to non‑extrafine beclometasone dry powder inhaler in terms of change from baseline in mean pre‑dose morning peak expiratory flow with no difference in adverse events. There are no published comparative studies at the higher licensed dose, or with other available ICS/LABA combination inhalers or studies with patient orientated primary outcomes.

Regulatory status: Fostair pressurised metered dose inhaler has been licensed in the UK since 2007. Fostair NEXThaler is a new dry powder formulation inhaler licensed for the regular treatment of asthma in adults aged 18 years and over where use of a combination product (ICS and LABA) is appropriate. It was launched in September 2014.

Effectiveness

  • In an 8‑week, double-blind, randomised controlled trial (RCT; n=755) in adults with stable asthma, extrafine beclometasone/formoterol 100/6 micrograms, 1 inhalation twice daily administered via a dry powder inhaler was non‑inferior to the pressurised metered dose inhaler in terms of change from baseline in mean pre‑dose morning peak expiratory flow.

  • In the same RCT, both extrafine formulations (dry powder and pressurised metered dose inhaler) of beclometasone/formoterol were statistically significantly superior to non‑extrafine beclometasone dry powder inhaler for the same outcome (p<0.001).

Safety

  • The summary of product characteristics (SPC) states that the most common adverse reaction with beclometasone/formoterol dry powder inhaler is tremor.

  • In an 8‑week RCT, 6 severe asthma exacerbations were observed in the non‑extrafine beclometasone group, 4 in the extrafine beclometasone/formoterol dry powder inhaler group and 3 in the extrafine beclometasone/formoterol pressurised metered dose inhaler group.

  • The proportion of people experiencing treatment emergent adverse events was low and similar across all 3 treatment groups. Adverse events included headache, nasopharyngitis and pharyngitis.

Patient factors

  • Fostair NEXThaler contains beclometasone in an extrafine particle formulation. Dose adjustment may be required if people are transferred to Fostair NEXThaler inhalation powder from other inhalers containing non‑extrafine beclometasone or different ICS medicines.

  • In a usability study with a number of limitations, more people preferred to use the NEXThaler device compared with Turbuhaler (Turbohaler) and Diskus (Accuhaler).

  • Extrafine beclometasone/formoterol dry powder inhaler has similar contraindications, cautions and interactions to other ICS/LABA combination inhalers.

  • No reliever treatments are available which use the NEXThaler device. Patients would therefore need to use a different inhaler device for their reliever and preventer medications. The British guideline on the management of asthma states this may lead to increased errors in inhaler use.

  • Unlike Fostair pressurised metered dose inhaler, Fostair NEXThaler is not licensed for maintenance and reliever therapy in adults with asthma.

Resource implications

  • The cost for 30‑days treatment with Fostair NEXThaler ranges from £14.66 to £29.32 depending on the dose.

  • The cost of other licensed ICS/LABA combination inhalers at approximately similar doses ranges from £14.66 to £38.00 depending on the dosage and the product. See the cost of treatment alternatives section for more information.

Introduction and current guidance

The British guideline on the management of asthma (SIGN guideline 141) recommends that ICS are the first‑choice regular preventer therapy for adults and children. If asthma is not adequately controlled on an ICS alone (at step 2), add‑on therapy may be needed (step 3). For adults and children aged 5 years and over, an ICS and a LABA should be considered.

If treatment with an ICS and LABA is considered appropriate, inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over (NICE technology appraisal guidance 138) recommends that using a combination inhaler within its marketing authorisation is an option. NICE recommends that the decision to use a combination inhaler or the 2 agents in separate inhalers should be made on an individual basis, taking into consideration therapeutic need and the likelihood of treatment adherence. If a combination inhaler is chosen, then the least costly device that is suitable for the individual is recommended.

The British guideline on the management of asthma recommends that in adults, administering ICS using a pressurised metered dose inhaler plus a spacer is as effective as using any dry powder inhaler. The guideline advises that there is no evidence to guide the order in which different devices should be tested in people who cannot use a pressurised metered dosed inhaler, and the most important points to consider are patient preference and cost. The person should have their ability to use an inhaler device assessed by a competent healthcare professional, and inhaler technique should be reassessed as part of a structured clinical review.

Full text of introduction and current guidance.

Product overview

Fostair NEXThaler (Chiesi Limited) is a dry powder inhaler containing 100 micrograms of beclometasone dipropionate (an ICS) and 6 micrograms of formoterol fumarate (a LABA).

The beclometasone in Fostair NEXThaler is an extrafine particle formulation, therefore dose adjustment is required when people are transferred to Fostair NEXThaler inhalation powder from a formulation with a non‑extrafine particle size distribution. People who are transferred to Fostair NEXThaler inhalation powder from Fostair pressurised metered dose inhaler do not need dose adjustment because both inhalers use the extrafine particle formulation.

Fostair NEXThaler is licensed for the regular treatment of asthma in adults aged 18 years and over where use of a combination product (ICS and LABA) is appropriate:

  • people not adequately controlled with ICS and 'as needed' inhaled short‑acting beta2‑agonist or

  • people already adequately controlled on both ICS and LABAs.

The recommended dosage of Fostair NEXThaler is 1−2 inhalations twice daily and the maximum daily dose is 4 inhalations daily. People should be advised to keep a separate short‑acting bronchodilator available at all times for the treatment of acute asthma attacks.

It should be noted that unlike Fostair pressurised metered dose inhaler; Fostair NEXThaler is not licensed for maintenance and reliever therapy in adults with asthma.

Fostair NEXThaler costs £29.32 for 1 inhaler containing 120 doses (MIMS, December 2014; excluding VAT).

Full text of product overview.

Evidence review

  • This evidence summary includes an RCT (Kanniess et al. 2014) that compared the efficacy and safety of extrafine beclometasone/formoterol dry powder inhaler (Fostair NEXThaler) at the lower licensed dose (1 inhalation twice daily) with extrafine beclometasone/formoterol pressurised metered dose inhaler (Fostair) and non‑extrafine beclometasone dry powder inhaler; and a study (Voshaar et al. 2014) that compared the usability of the NEXThaler device with a Turbuhaler (Turbohaler) and Diskus (Accuhaler) device.

  • Kanniess et al. (2014) was an 8‑week, double‑blind RCT in 755 adults with stable asthma. The study found that extrafine beclometasone/formoterol dry powder inhaler (Fostair NEXThaler) was non‑inferior to the same combination administered by pressurised metered dose inhaler (Fostair) for the primary outcome of change from baseline in mean pre‑dose morning peak expiratory flow (mean difference between the dry powder and pressurised metered dose inhaler groups −1.84 litres/minute, 95% confidence interval [CI] −6.73 to 3.05). Both extrafine formulations (dry powder and pressurised metered dose inhaler) of beclometasone/formoterol were statistically significantly superior to non extrafine beclometasone dry powder inhaler for the same outcome (p<0.001). Some secondary patient orientated outcomes statistically significantly improved in both the extrafine beclometasone/formoterol dry powder groups compared with non‑extrafine beclometasone alone, as would be expected. However there were no statistically significant differences for patient‑orientated outcomes between the 2 extrafine beclometasone/formoterol groups.

  • Voshaar et al. (2014) was a randomised crossover study that investigated the usability of the NEXThaler device, compared with 2 other dry powder inhalers in 66 adults with asthma and no previous experience of using dry powder inhalers. The study did not consider active treatment, had a number of limitations and is not considered in detail in this evidence summary. Statistically significantly more participants reported that if they had to pick one of the devices to use every day, they would choose NEXThaler (75.4%) compared with an Accuhaler (16.9%; p<0.001) or a Turbohaler (7.7%; p<0.001).

  • In Kanniess et al. (2014), 26 asthma exacerbations were reported during the trial, 13 of which were classed as severe. Of these, 6 were observed in the non‑extrafine beclometasone group, 4 in the extrafine beclometasone/formoterol dry powder inhaler group and 3 in the extrafine beclometasone/formoterol pressurised metered dose inhaler group. The percentage of people reporting treatment‑emergent adverse events was low in all 3 treatment groups (0.8% in the beclometasone/formoterol dry powder inhaler group and 1.2% in both the extrafine beclometasone/formoterol pressurised metered dose inhaler and non‑extrafine beclometasone groups). Treatment‑emergent adverse events reported in the extrafine beclometasone/formoterol dry powder inhaler, beclometasone/formoterol pressurised metered dose inhaler group and non‑extrafine beclometasone groups included headache (1, 4 and 5 people respectively), nasopharyngitis (2, 6 and 6 people respectively) and pharyngitis (7, 3 and 2 people respectively).

  • The SPC reports that the most common adverse reaction with beclometasone/formoterol dry powder inhaler is tremor. The SPC states that in a 12‑week trial, tremor was mild in intensity, was only observed with the higher dosage (2 inhalations twice daily) and occurred most frequently at the beginning of treatment.

  • Kanniess et al. (2014) was a large RCT (n=755). The primary outcome of this study, change from baseline to the entire 8‑week treatment period in average pre‑dose morning peak expiratory flow, was a disease orientated outcome. Patient orientated effects such as asthma symptoms and asthma control questionnaire score were reported as secondary outcomes. This study investigated the lower licensed dosage (1 inhalation twice daily) of extrafine beclometasone/formoterol dry powder inhaler. There are no published studies investigating the higher licensed dosage (2 inhalations twice daily) and so the efficacy and safety of this dosage cannot be determined from the available published evidence.

Full text of evidence review.

Context

Six ICS/LABA combination inhalers are licensed in the UK for treating asthma (see the relevant summaries of product characteristics for more information):

  • extrafine beclometasone/formoterol (Fostair) metered dose inhaler and dry powder inhaler

  • budesonide/formoterol (DuoResp Spiromax) dry powder inhaler

  • budesonide/formoterol (Symbicort) dry powder inhaler

  • fluticasone furoate/vilanterol (Relvar Ellipta) dry powder inhaler

  • fluticasone propionate/formoterol (Flutiform) metered dose inhaler

  • fluticasone propionate/salmeterol (Seretide) metered dose inhaler and dry powder inhaler.

Full text of context.

Estimated impact for the NHS

Extrafine beclometasone/formoterol administered using a dry powder inhaler (Fostair NEXThaler) has been shown to be non‑inferior to the pressurised metered dose inhaler (Fostair) for a disease orientated outcome (change in peak expiratory flow). However there are no published comparative studies with the higher licensed dose or with other available ICS/LABA combination inhalers or studies with patient orientated primary outcomes. Unlike some other ICS/LABA combination inhalers, Fostair NEXThaler is only licensed for use in adults aged 18 years and above. In addition, Fostair NEXThaler is not licensed for maintenance and reliever therapy in adults with asthma.

The British guideline on the management of asthma recommends that for adults, a pressurised metered dose inhaler plus a spacer is as effective as any dry powder inhaler for administering ICS. For people who cannot use a pressurised metered dose inhaler, the guideline advises that the most important points to consider are patient preference and cost, and the choice of device may be determined by the choice of drug.

The British guideline on the management of asthma advises that using the same type of device to deliver preventer and reliever treatments may improve outcomes. Currently, no reliever medications are available in the NEXThaler device, whereas for some other ICS/LABA dry powder inhaler devices (such as Accuhaler and Turbohaler) there are reliever inhalers available using the same device.

Local decision makers will need to consider the available evidence on efficacy and safety, as well as cost and individual patient factors, when making decisions about using extrafine beclometasone/formoterol dry powder inhaler (NEXThaler) or another ICS/LABA combination inhaler.

Full text of estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.